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Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease.
FEBS Open Bio. 2020 06; 10(6):995-1004.FO

Abstract

A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (Mpro , also called 3-chymotrypsin-like protease) of SARS-CoV-2 is a potential target for treatment of COVID-19. A Mpro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic α-ketoamide inhibitors, which were previously disconnected from each Cys145 of the Mpro homodimer, and energy calculations were performed. Structure-based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with Mpro . Additional docking simulations for predicted compounds with high binding affinity with Mpro suggested that 28 bioactive compounds may have potential as effective anti-SARS-CoV-2 drug candidates. The procedure used in this study is a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.

Authors+Show Affiliations

Institute of Molecular Function, Misato-shi, Saitama, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32374074

Citation

Tsuji, Motonori. "Potential anti-SARS-CoV-2 Drug Candidates Identified Through Virtual Screening of the ChEMBL Database for Compounds That Target the Main Coronavirus Protease." FEBS Open Bio, vol. 10, no. 6, 2020, pp. 995-1004.
Tsuji M. Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. FEBS Open Bio. 2020;10(6):995-1004.
Tsuji, M. (2020). Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. FEBS Open Bio, 10(6), 995-1004. https://doi.org/10.1002/2211-5463.12875
Tsuji M. Potential anti-SARS-CoV-2 Drug Candidates Identified Through Virtual Screening of the ChEMBL Database for Compounds That Target the Main Coronavirus Protease. FEBS Open Bio. 2020;10(6):995-1004. PubMed PMID: 32374074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. A1 - Tsuji,Motonori, Y1 - 2020/05/29/ PY - 2020/03/31/received PY - 2020/04/21/revised PY - 2020/05/02/accepted PY - 2020/5/7/pubmed PY - 2020/6/20/medline PY - 2020/5/7/entrez KW - 2019 novel coronavirus KW - COVID-19 KW - Mpro KW - SARS-CoV-2 KW - drug repositioning KW - virtual screening SP - 995 EP - 1004 JF - FEBS open bio JO - FEBS Open Bio VL - 10 IS - 6 N2 - A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (Mpro , also called 3-chymotrypsin-like protease) of SARS-CoV-2 is a potential target for treatment of COVID-19. A Mpro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic α-ketoamide inhibitors, which were previously disconnected from each Cys145 of the Mpro homodimer, and energy calculations were performed. Structure-based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with Mpro . Additional docking simulations for predicted compounds with high binding affinity with Mpro suggested that 28 bioactive compounds may have potential as effective anti-SARS-CoV-2 drug candidates. The procedure used in this study is a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning. SN - 2211-5463 UR - https://www.unboundmedicine.com/medline/citation/32374074/Potential_anti_SARS_CoV_2_drug_candidates_identified_through_virtual_screening_of_the_ChEMBL_database_for_compounds_that_target_the_main_coronavirus_protease_ L2 - https://doi.org/10.1002/2211-5463.12875 DB - PRIME DP - Unbound Medicine ER -